DESCRIPTION: (Principal Investigator's Abstract) The major objective in this research is to make significant contributions to organic chemistry and medicine through chemical studies on physiologically active natural and man-made organic compounds. Organic synthesis plays the major role in all of the proposed research topics, including: 1. stereochemical assignment of acyclic compounds through organic synthesis (universal spectroscopic database creation, mycolactone, australifungin, tethered maitotoxin analogs, and others); 2. total synthesis of pinnatoxins and related natural products (pinnatoxins B and C, spirolides, gymnodimine, azaspiracid, immobilized pinnatoxins, and others); 3. covalently cross-linked Watson-Crick base pair models; 4. conformational analysis of C-and O-glycopyranosides (human blood antige, lactose, synthetic 3-O-methyl-D-mannose-containing polysaccarides (MMP), and others); 5. immobilized tetrodotoxin; 6. total synthesis of batrachotoxin, aranotin, and YW3699. We believe that the power of organic chemistry is most effectively extended by challenging these complex systems, and much of the progress of medicine critically depends upon the extension of the power of organic chemistry. It is also our specific objective to develop practical and efficient syntheses of certain natural products and their analogs, which have high physiological activity, but are not available in appreciable amounts from natural sources. These studies are again expected to stimulate progress in medicine.